THE ANTI-TUMOR EFFECT OF ENDOGENOUS ENDOSTATIN PRODUCED BY THE HUMAN CELL LINE

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概要

• 論文の詳細を見る

• Background: Endostatin, C-terminal fragment of collagen XVIII, has been reported to be an angiogenic inhibitor and is currently undergoing clinical trials as a new anticancer drug in USA. However, the mechanism that endostatin inhibits angiogenesis is still unknown. Our aim was to elucidate whether endostatin had anti-tumor activity in hepatocellular carcinoma (HCC). Method: We transplanted human HCC cells (JHH-1) into nude mice to develop solid tumors and administrated anti-endostatin antibody (CH18B). The antibody was established against synthetic peptides of human endostatin and confirmed to be specific for human molecule. We daily injected CH18B and an irrelevant IgG2a monoclonal antibody (control), weekly measured tumor size and resected tumors after 4weeks. The expression and localization of human endostatin in the tumors were examined immunohistochemically. The apoptotic and the proliferative index were assessed by TUNEL method and anti-phosphorylated histone H3 monoclonal antibody, respectively. Results: In western blot analysis, it realized that JHH-1 produced the protein detected with CH18B. CH18B-treated mice had significantly larger tumors (CH18B: 533 ± 142 mm3 vs. control: 257±44 mm3; p<0.01 at day 28) and developed more capillaries on the tumor surfaces. Human endostatin localized at basement membranes between the tumor and the stroma. The number of apoptotic cells treated with CH18B was significantly lesser (p<0.01), whereas there was no difference in the HCC cell proliferation. Conclusions: Anti-endostatin antibody inhibited the induction of apoptosis by blocking endogenous endostatin and promotes tumor growth. This is the first report of the anti-tumor effect of endogenous endostatin produced by the human HCC cell line by the novel way.

• 日本結合組織学会の論文

著者

• 二宮 善文

  岡山大学大学院 医歯薬学総合研究科 分子医化学

• 二宮 善文

  重井医学研究所

• 二宮 善文

  岡山大学大学院医歯学総合研究科分子医化学

• 二宮 善文

  重井医学研究所 超微病理

• 二宮 善文

  岡山大学 第2解剖

• 米澤 朋子

  Okayama Univ. Graduate School Of Medicine Dentistry And Pharmaceutical Sci.

• Sado Y

  Shigei Medical Research Institute

• Sado Yoshikazu

  Shigei Medical Research Institute

• Sado Yoshikazu

  Divisions Of Immunology And Ultrastructure Research Shigei Medical Research Institute

• Tomono Yasuko

  Shigei Medical Institute

• Ninomiya Y

  Department Of Molecular Biology And Biochemistry Okayama University Graduate School Of Medicine Dent

• Naito Ichiro

  Shigei Med. Res. Inst., Okayama Univ. Grad. Sch. Med. and Dent.

• Tsuboi So

  Shigei Med. Res. Inst., Okayama Univ. Grad. Sch. Med. and Dent.

• Manabe Koji

  Shigei Med. Res. Inst., Okayama Univ. Grad. Sch. Med. and Dent.

• Ohmori Hiroyuki

  Shigei Med. Res. Inst., Okayama Univ. Grad. Sch. Med. and Dent.

• Miyazaki Masahiro

  Shigei Med. Res. Cell Biol., Okayama Univ. Grad. Sch. Med. and Dent.

• Ninomiya Yoshifumi

  Shigei Med. Res. Mol. Biol. Biochem., Okayama Univ. Grad. Sch. Med. and Dent.

• Tomono Y

  Department Of Gastroenterological Surgery Transplant And Surgical Oncology Okayama University Gradua

• Ninomiya Yoshifumi

  Department Of Molecular Biology And Biochemistry Okayama University Graduate School Of Medical Schoo

• 二宮 善文

  岡山大学大学院医歯学総合研究科(分子医化学)

• Miyazaki Masahiro

  Shigei Med. Res. Cell Biol. Okayama Univ. Grad. Sch. Med. And Dent.

• Tsuboi So

  Shigei Med. Res. Inst. Okayama Univ. Grad. Sch. Med. And Dent.

• Manabe Koji

  Shigei Med. Res. Inst. Okayama Univ. Grad. Sch. Med. And Dent.

• Naito Ichiro

  Department Of Human Morphology Okayama University Graduate School Of Medicine Dentistry And Pharmace

• Ohmori Hiroyuki

  Shigei Med. Res. Inst. Okayama Univ. Grad. Sch. Med. And Dent.

• Naito Ichiro

  Division Of Immunology Shigei Medical Research Institute

• Ninomiya Yoshifumi

  Department Of Molecular Biology And Biochemistry Okayama University Graduate School Of Medicine Dent

• Sado Y

  Division Of Immunology Shigei Medical Research Institute

• Naito Ichiro

  Department Of Human Morphology Okayama University Graduate School Of Medicine Dentistry And Pharmace

• Naito I

  Department Of Human Morphology Okayama University Graduate School Of Medicine Dentistry And Pharmace

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